Tetrahydrofuran → 5-(4'-diethoxymethyl-biphenyl-2-yl)-2-(tetrahydropyran-2-yl)-2H-tetrazole

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Reaction Conditions

Reaction Steps

In another flask, dichloro[1,3bis(diphenylphosphino)propane]nickel(II) (0.027 g; 0.05 mmol) is suspended in tert-butyl methyl ether (3.8 mL) and cooled to about 0° C. before a 0.5 M solution of zinc chloride in tetrahydrofuran (0.50 mL; 0.25 mmol) and a solution of a mixture of 5-(2-chlorophenyl)-2-(tetrahydropyran-2-yl)-2H-tetrazole and 5-(2-chlorophenyl)-1-(tetrahydropyran-2-yl)-1H-tetrazole (1.32 g; 5.0 mmol) in tert-butyl methyl ether (1.3 mL) are added. To the vigorously stirred resulting suspension is added at about 0° C. 13 mL of the above 0.46 M 4-(diethoxymethyl)phenylmagnesium bromide solution (6.0 mmol) over one hour. The resulting black-yellow solution is stirred at about 0° C. for 5 hours, allowed to warm up and further stirred at room temperature for 19 hours. The mixture is cooled to about 0° C. and quenched with a 7.5% solution of ammonium chloride in water (10 mL). The aqueous phase is separated and extracted with ethyl acetate (25 mL). The combined organic phases are washed with water (10 mL), a 7.5% solution of sodium carbonate in water (10 mL) and a 10% solution of sodium chloride in water (10 mL). The combined organic phases are evaporated in vacuo. A solution of the resulting brown-yellow oil in a small amount of ethyl acetate is filtered and evaporated. The resulting oil (2.68 g) is purified by column chromatography on silica gel eluting with a 1:4 mixture of ethyl acetate and hexane (in the presence of 0.2 volume-% of triethylamine) to afford the main isomer (N2-isomer) 5-(4′-diethoxymethyl-biphenyl-2-yl)-2-(tetrahydro-pyran-2-yl)-2H-tetrazole as a colorless oil.

Provenance & Evidence